To date, approximately 500 iatrogenic Creutzfeldt-Jakob disease cases have been reported worldwide, most of them resulting from cadaveric dura mater graft and from the administration of prion-contaminated human growth hormone. The unusual resistance of prions to decontamination processes, their large tissue distribution, and the uncertainty about the prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the general population lead to specific recommendations regarding identification of tissue at risk and reprocessing of reusable medical devices, including the use of dedicated treatment for prion inactivation. We previously described an in vitro assay, called Surf-PMCA, which allowed us to classify prion decontamination treatments according to their efficacy on vCJD prions by monitoring residual seeding activity (RSA). Here, we used a transgenic mouse line permissive to vCJD prions to study the correlation between the RSA measured in vitro and the in vivo infectivity. Implantation in mouse brains of prion-contaminated steel wires subjected to different decontamination procedures allows us to demonstrate a good concordance between RSA measured by Surf-PMCA (in vitro) and residual infectivity (in vivo). These experiments emphasize the strength of the Surf-PMCA method as a rapid and sensitive assay for the evaluation of prion decontamination procedures and also confirm the lack of efficacy of several marketed reagents on vCJD prion decontamination.IMPORTANCE Creutzfeldt-Jakob diseases are neurodegenerative disorders for which transmission linked to medical procedures have been reported in hundreds of patients. As prion diseases, they are characterized by an unusual resistance to conventional decontamination processes. Moreover, their large tissue distribution and the ability of prions to attach to many surfaces raised the risk of transmission in health care facilities. It is therefore of major importance that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated for prion inactivation. We previously described an in vitro assay, which allowed us to classify accurately prion decontamination treatments according to their efficacy on variant Creutzfeldt-Jakob disease. The significance of this study is in demonstrating the concordance between previous in vitro results and infectivity studies in transgenic mice. Furthermore, commercial reagents currently used in hospitals were tested by both protocols, and we observed that most of them were ineffective on human prions.

中文翻译：

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变异克雅氏病净化研究中生物测定与蛋白质错误折叠循环扩增之间的相关性。


迄今为止，全世界已报告约 500 例医源性克雅氏病病例，其中大多数是由尸体硬脑膜移植和施用受朊病毒污染的人类生长激素引起的。朊病毒对净化过程的异常抵抗力、其大的组织分布以及普通人群中变异型克雅氏病（vCJD）患病率的不确定性导致了关于识别有风险的组织和再处理可重复使用的医疗设备的具体建议，包括使用专门的治疗方法来灭活朊病毒。我们之前描述了一种名为 Surf-PMCA 的体外测定，它使我们能够通过监测残留播种活性 (RSA)，根据对 vCJD 朊病毒的功效对朊病毒净化治疗进行分类。在这里，我们使用允许 vCJD 朊病毒的转基因小鼠品系来研究体外测量的 RSA 与体内感染性之间的相关性。将经过不同净化程序的受朊病毒污染的钢丝植入小鼠大脑中，我们可以证明 Surf-PMCA（体外）测量的 RSA 与残留感染性（体内）之间具有良好的一致性。这些实验强调了 Surf-PMCA 方法作为评估朊病毒净化程序的快速、灵敏检测方法的优势，并证实了几种市售试剂对 vCJD 朊病毒净化缺乏功效。 重要性 克雅氏病是一种神经退行性疾病，其中据报道，数百名患者中存在与医疗程序有关的传播。作为朊病毒疾病，它们的特点是对传统净化过程具有异常的抵抗力。 此外，它们的大组织分布和朊病毒附着在许多表面的能力增加了医疗机构中传播的风险。因此，在医疗器械再加工之前对其应用的净化程序要经过彻底的朊病毒灭活验证，这一点非常重要。我们之前描述了一种体外测定，它使我们能够根据朊病毒净化治疗对变异型克雅氏病的功效进行准确分类。这项研究的意义在于证明了先前的体外结果与转基因小鼠的感染性研究之间的一致性。此外，目前医院使用的商业试剂经过这两种方案的测试，我们观察到其中大多数对人类朊病毒无效。